Description:
Cancer metastasis are responsible for ~90% of cancer associated deaths. Recent studies suggest that immune cells play critical roles in promoting metastasis, especially myeloid cells from the bone marrow. UTHealth researchers, with researchers from The Methodist Hospital, observed a highly conserved expression of S100A4 in immune suppressive myeloid cells in all cancers. They created and engineered monoclonal antibodies against S100A4 and showed that the S100A4 antibodies suppressed breast cancer metastasis to the lung in two different mouse models.
Background
Cancer is a leading cause of death in the United States and worldwide. Thanks to the development in earlier diagnosis and effective therapies, the overall survival for some cancers, such as breast and colon cancer, has increased significantly in the last decade. However, only limited progress has been made to treat cancer metastasis, which accounts for ~ 90% of cancer-related deaths. Tumor-associated myeloid cells are critical regulators of tumor progression, metastasis, and immune evasion. Through a multi-regional and multi-dimensional analyses of human gliomas and immune cells at the single cell level, S100A4 is nominated as a promising therapeutic target for therapeutic treatment of metastatic diseases.
Significance and Impact
S100A4 expression is associated with worse survival in many cancers, and S100A4 is highly expressed in immune suppressive myeloid and T cells in human gliomas. UTHealth pioneering scientists created and generated S100A4 targeting monoclonal antibodies (Abs). Previous studies showed that deletion of S100A4 in the tumor microenvironment significantly increases survival in mouse models of glioma. The S100A4 monoclonal Abs exhibited similar results as previous studies that blocking extracellular S100A4 suppresses metastasis but not primary tumor growth. Thus, S100A4 monoclonal antibodies are potentially a promising therapeutic strategy for treating or preventing cancers.
Technology Highlights
- S100A4 antibody suppresses spontaneous lung metastasis in the MMTV-PyMT mouse model.
- S100A4 antibody also modulates the frequency of M-MDSCs and PMN-MDSCs in the blood and lung metastasis, respectively.
- S100A4 antibody treatment suppresses lung metastasis by inhibiting the metastatic niche formation.
Potential Applications
During the metastatic process, primary tumor cells must leave the original primary tumor, intravasate into blood vessel, survive and migrate in the circulation, extravasate into secondary tissue, and arrest in capillary bed and proliferate. For triple negative breast cancer, the only FDA approved treatment for the metastatic disease is an immune checkpoint inhibitor, Pembrolizumab. The novel S100A4 targeting mAb is the next highly promising strategy for therapeutic treatment of metastatic diseases.
Related Publication: Abdelfattah et al. Nat. Commun. 13, 767 (2022)
Intellectual Property Status
Patent application filed, available for licensing.
About the Inventors
Zhiqiang An, Ph.D.
Vice President of Drug Discovery at UTHealth Houston
Ningyan Zhang, Ph.D.
Professor at UTHealth Houston and Co-Director of the CPRIT Therapeutic Antibody Core.
Kyuson Yun, Ph.D.
Houston Methodist Chair in Neurodegenerative Disease Research, Stanley H. Appel Department of Neurology